An increase in the carbon dioxide concentration in arterial blood caused by disease or altered environment has a profound effect on breathing. The brain stem chemoreceptors thought to be primarily responsible are stimulated by hydrogen ion changes resulting from the reaction of CO2 with water in the tissue. This study is based on the hypothesis that catalysis of CO2 hydration by carbonic anhydrase in glial cells and transport of the resulting bicarbonate ions across the cellmembranes by a specific anion carrier system are cardinal steps in the function of the chemoreceptors. We propose to evaluate this hypothesis by experiments in anesthetized rats to measure the respiratory response to CO2. Inhibitors of catalysis and bicarbonate transport will be administered by perfusing the cerebrospinal fluid space of the brain stem. The parameters of a theoretical model of CO2 transport which includes the hydration reaction and carrier mediated HCO3 transport can then be statistically estimated from the experimental data and compared before and after inhibition of catalysis and transport. The results of this study will provide an understanding of the early events in the homeostasis of the brain acid-base environment and its effects on control of breathing.